Local Consolidative Therapy May Have Prominent Clinical Efficacy in Patients with EGFR-Mutant Advanced Lung Adenocarcinoma Treated with First-Line Afatinib

SIMPLE SUMMARY: Afatinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) used to treat patients with advanced EGFR-mutant lung cancer. In this study, we retrospectively enrolled patients with lung adenocarcinomas harboring susceptible EGFR mutations, who were diagnosed and treated with first-line afatinib in three Kaohsiung Medical University-affiliated hospitals. Patients who received local consolidative therapy (LCT) had a significantly longer PFS than those who did not. Patients who received LCT also had significantly longer OS. Multivariable analysis showed LCT was an independent prognostic factor for improved PFS and OS. The analyses using propensity score-weighting showed consistent results. We conclude that LCT may improve clinical outcomes, in terms of PFS and OS, in patients with advanced EGFR-mutant lung adenocarcinomas who are treated with first-line afatinib. Further large-scale prospective trials are warranted. ABSTRACT: Afatinib is an irreversible tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR), which is utilized for the treatment of patients with advanced lung cancer that harbors EGFR mutations. No studies have evaluated the clinical efficacy of LCT in patients treated with first-line afatinib. In this study, we retrospectively enrolled patients with advanced lung adenocarcinomas harboring susceptible EGFR mutations who were diagnosed and treated with first-line afatinib in three hospitals. A total of 254 patients were enrolled, including 30 (12%) patients who received LCT (15 patients received definitive radiotherapy for the primary lung mass and 15 patients received curative surgery). Patients who received LCT had a significantly longer PFS than those who did not (median PFS: 32.8 vs. 14.5 months, p = 0.0008). Patients who received LCT had significantly longer OS than those who did not (median OS: 67.1 vs. 34.5 months, p = 0.0011). Multivariable analysis showed LCT was an independent prognostic factor for improved PFS (adjusted hazard ratio [aHR] [95% confidence interval (CI)]: 0.44 [0.26–0.73], p = 0.0016) and OS (aHR [95% CI]: 0.26 [0.12–0.54], p = 0.0004). The analyses using propensity score-weighting showed consistent results. We conclude that LCT may improve clinical outcomes, in terms of PFS and OS, in patients with advanced EGFR-mutant lung adenocarcinomas who are treated with first-line afatinib.